An integrated approach for the in vitro dosimetry of engineered nanomaterials.
An integrated approach for the in vitro dosimetry of engineered nanomaterials.
复制标题
DOI：
10.1186/1743-8977-11-20
复制
发表时间：
2014-05-01
影响因子：
10
通讯作者：
Demokritou P
中科院分区：
文献类型：
--
作者：
Cohen JM;Teeguarden JG;Demokritou P
非常需要能够快速评估纳米材料毒性的筛选工具。发展可靠的体外筛选方法的一个障碍是需要精确测量细胞剂量。我们在这里提出了一种方法，能够准确地确定传递到细胞的剂量度量。该方法包括：（1）工程纳米材料（ENM）悬浮液制备的标准化;（2）控制向培养细胞递送的ENM特性的测量;以及（3）使用ISDD模型计算作为暴露时间函数的递送剂量。该方法对实验测得的剂量进行了验证，并简化了解析表达式的传递剂量（相关的体外剂量（RID）f函数）推导出20个ENM。纳米毒理学家可以使用这些函数来准确计算总质量（RIDM），表面积（RIDSA）或颗粒数（RIDN）作为暴露时间的函数传递到细胞。所提出的方法被用来获得有效的密度，团聚体直径和RID功能的17个工业相关的金属和金属氧化物ENM，两个碳纳米颗粒，和非团聚的金纳米球，两个孔板配置（96和384孔板）。对于附聚ENM，测量的有效密度平均比材料密度低60%。我们报告了递送剂量度量的巨大变化，一些材料在24小时内沉积，而另一些材料需要超过100小时才能递送到细胞。采用中子活化示踪粒子系统来验证一些ENM的拟定体外剂量测定方法（测得的递送至细胞剂量在估计值的9%以内）。我们的研究结果证实并扩展了实验和计算证据，即聚集特性会影响传递给细胞的剂量。因此，测量这些特性对于有效使用纳米毒理学体外系统至关重要。这里提出和验证的细胞剂量测定的混合实验/计算方法可用于纳米毒理学家准确计算各种ENM和体外条件下作为暴露时间函数的细胞剂量指标。实验人员可以使用本文中介绍的广泛使用的ENM的RID函数和表征数据来设计和解释毒性研究。
There is a great need for screening tools capable of rapidly assessing nanomaterial toxicity. One impediment to the development of reliable in vitro screening methods is the need for accurate measures of cellular dose. We present here a methodology that enables accurate determination of delivered to cell dose metrics. This methodology includes (1) standardization of engineered nanomaterial (ENM) suspension preparation; (2) measurement of ENM characteristics controlling delivery to cells in culture; and (3) calculation of delivered dose as a function of exposure time using the ISDD model. The approach is validated against experimentally measured doses, and simplified analytical expressions for the delivered dose (Relevant In Vitro Dose (RID)f function) are derived for 20 ENMs. These functions can be used by nanotoxicologists to accurately calculate the total mass (RIDM), surface area (RIDSA), or particle number (RIDN) delivered to cells as a function of exposure time. The proposed methodology was used to derive the effective density, agglomerate diameter and RID functions for 17 industrially-relevant metal and metal oxide ENMs, two carbonaceous nanoparticles, and non-agglomerating gold nanospheres, for two well plate configurations (96 and 384 well plates). For agglomerating ENMs, the measured effective density was on average 60% below the material density. We report great variability in delivered dose metrics, with some materials depositing within 24 hours while others require over 100 hours for delivery to cells. A neutron-activated tracer particle system was employed to validate the proposed in vitro dosimetry methodology for a number of ENMs (measured delivered to cell dose within 9% of estimated). Our findings confirm and extend experimental and computational evidence that agglomerate characteristics affect the dose delivered to cells. Therefore measurement of these characteristics is critical for effective use of in vitro systems for nanotoxicology. The mixed experimental/computational approach to cellular dosimetry proposed and validated here can be used by nanotoxicologists to accurately calculate the delivered to cell dose metrics for various ENMs and in vitro conditions as a function of exposure time. The RID functions and characterization data for widely used ENMs presented here can together be used by experimentalists to design and interpret toxicity studies.
登录
查看更多内容
影响因子：
10
作者：
Hinderliter PM;Minard KR;Orr G;Chrisler WB;Thrall BD;Pounds JG;Teeguarden JG
通讯作者：
Teeguarden JG
DOI：
10.1080/10937404.2010.483176
发表时间：
2010-02
期刊：
Journal of toxicology and environmental health. Part B, Critical reviews
影响因子：
--
作者：
Krewski D;Acosta D Jr;Andersen M;Anderson H;Bailar JC 3rd;Boekelheide K;Brent R;Charnley G;Cheung VG;Green S Jr;Kelsey KT;Kerkvliet NI;Li AA;McCray L;Meyer O;Patterson RD;Pennie W;Scala RA;Solomon GM;Stephens M;Yager J;Zeise L
通讯作者：
Zeise L
影响因子：
5
作者：
Bello, Dhimiter;Martin, John;Demokritou, Philip
通讯作者：
Demokritou, Philip
影响因子：
5
作者：
Cohen J;Deloid G;Pyrgiotakis G;Demokritou P
通讯作者：
Demokritou P
影响因子：
10.8
作者：
Khanbeigi, Raha Ahmad;Kumar, Abhinav;Collins, Helen
通讯作者：
Collins, Helen